Sickle cell disease, also referred to as sickle cell anemia, is an autosomal recessive genetic disease caused by an abnormality of the hemoglobin contained in the red blood cells, more specifically a structural abnormality of the β-chain of hemoglobin, characterized by the mutation of an amino acid of this β-chain, from glutamic acid to valine.
Sickle cell disease constitutes the most significant hemoglobinopathy throughout the world. Close to 120 million individuals are indeed thought to be carriers of the sickle cell trait.
Sickle cell disease is found in certain regions of the Indian subcontinent, in South America and in the Mediterranean basin. Intertropical Africa, that is to say the area located between the 15th parallel south and the 20th parallel north, is the most affected, with a rate of approximately one case of sickle cell disease per 65 births. The most affected countries are the Democratic Republic of the Congo, Senegal, Benin, and Angola. Mention may be made of a correlation, in these zones, with resistance to malaria, which supports the hypothesis that sickle cell disease would result from a process of natural selection by resistance to malaria, due to the difficulty for the plasmodium to carry out its cycle in sickle cells.
In France, homozygous sickle cell disease represents one birth in 1200. It is the primary genetic risk in Ile de France. In the West Indies, the rate reaches 1 case in 260 births. Sickle cell disease also affects the afro-American population, which is easily explained by the historical origin of the birth of this community in the United States, namely the mass of deportation of Africans in the context of the triangular trade, the descendents of whom remain nowadays affected by sickle cell disease.
Sickle cell disease thus constitutes a real public health problem, all the more since healthy carriers, who show no clinical sign, may be unaware that they are capable of transmitting this disease to their offspring. The World Health Organization predicts that, in a few decades, the number of carriers of such a hemoglobin abnormality will reach a rate of 8% of the worldwide population.
At the current time, there are several tests for testing for or diagnosing sickle cell disease. These tests are in particular based on the particular properties of the abnormal hemoglobin, termed hemoglobin S. These properties are for example, in the deoxygenated state, a decrease in solubility and a change in shape, called sickling. Under hypoxic conditions, the hemoglobin of the red blood cells undergoes gelling, and polymerizes into fibers which deform the red blood cells by elongating it, thereby giving it the appearance of a sickle.
The abnormal sickle nature of the hemoglobin can thus be detected by an insolubility test, termed Itano test, or by a hypoxia-induced sickling test, such as Emmel's test. More specifically, Emmel's test, well known to those skilled in the art, consists in bringing a blood sample into contact with a reducing agent, so as to trigger the phenomenon of sickling of the sickle red blood cells, and in observing under a microscope the effect of this agent on the shape of the red blood cells. However, these tests require specific laboratory equipment. In addition, they are not automatable.
Other identification tests currently used are based on electrophoresis techniques, high performance liquid chromatography (HPLC) techniques or molecular biology techniques, in particular techniques for detecting the disappearance of a restriction site in the nucleotide sequence of hemoglobin, or polymerase chain reaction (PCR) techniques. In addition to the fact that these tests require specific and expensive equipment, and also operator expertise, they are lengthy to carry out.